A number of diagnostic tests are routinely performed on humans to evaluate the amount or existence of analytes present in blood or other body fluids. These diagnostic tests typically rely on physiological fluid samples removed from a subject, either using a syringe or by pricking the skin.
PCT Publication No. WO 96/00110, published Jan. 4 Jan. 1996, describes an iontophoretic apparatus for transdermal monitoring of a target analyte, wherein an iontophoretic electrode is used to move the analyte into a collection reservoir and a biosensor is used to detect the analyte. In U.S. Pat. No. 5,279,543 to Glikfeld, iontophoresis is used to sample a substance through skin and into a receptacle on the skin surface. Glikfeld suggests that this sampling procedure can be coupled with a glucose-specific biosensor or glucose-specific electrodes in order to monitor blood glucose. Additionally, U.S. Pat. Nos. 5,362,307 and 5,730,714 both to Guy, et al. describe sampling devices.
Analytical biosensors have been embraced during the last decade as a means of combining the advantages of electrochemical signal transduction with the specificity inherent in biological interactions. However, two factors that may affect the quality of the data generated by the signal transduction are as follows. First, compounds unrelated to the analyte of interest may enter the analytical system and interact directly with the electrode assembly, leading to signal generation unrelated to the concentration of the analyte or its derivatives. These interfering species may be introduced either during manufacture of the biosensor or during its use. For example, certain compounds present in sample fluid (e.g., acetominophen and uric acid) are electrochemically “active” and are capable of signal generation independent of the specific biological system employed by the biosensor, via a direct interaction with the electrode. Additionally, compounds that may interact at an electrode may have been introduced during manufacturing for specific purposes, such as to provide antimicrobial or antifungal activity (biocides). These interfering species may produce overlapping current signals, thus decreasing the selectivity of the biosensor. Additionally, the compounds may irreversibly bind to the reactive face of the electrode assembly, leading to fouling of the sensing surface and reduced sensitivity.
Several techniques have been employed to minimize the effects of interfering species on electrode function to get around these issues. One technique is to use the lowest polarizing voltage sufficient for the intended reaction. This reduces the current (i.e., electrons) generated by any undesired electrochemical oxidations requiring polarizing voltages higher than what is required for the intended reaction. However, because some enzymatic systems employed in biosensors require voltage levels that do not provide sufficient screening of signals generated by interfering species, the voltage level cannot be decreased below that which allows generation of signals from the interfering species.
A second technique has been to construct membranes or other physical barriers to impede the interfering species from reaching the face of the electrode. The list of films which may be employed includes cellulose acetate, poly(o-phenylenediamine), polyphenol, polypyrrole, polycarbonate, and Nafion® (E.I du Pont de Nemours & Co., Wilmington Del.) polymer. However, such membranes can be difficult to prepare and may not efficiently attach to the reactive surface of the electrode. There remains a need in the art for methods and devices which provide an efficient reduction of interfering species while maintaining efficient detection of an analyte.